KB220Z A PRO-DOPAMINE REGULATOR, BALANCES BRAIN REWARD CIRCUITRY INDUCING “HOMEOSTASIS.”

Kenneth Blum, Ph.D., DHL, John Giordano, MAC, DHL and Lyle Fried, CAP, ICADC, CHC

KB220Z A PRO-DOPAMINE REGULATOR, BALANCES BRAIN REWARD CIRCUITRY INDUCING “HOMEOSTASIS.”

Today we are facing the worst opiate /opioid epidemic in American History with 127 people dying every day from a narcotic overdose. It has been estimated that at least 27 million Americans are hooked on opiates/opioids. While making the anti- opiate drug Naloxone available without a prescription as an antidote for people who stop breathing is good, the underlying problem is that less than 25% of addicted Americans are being treated for their narcotic addiction. Providing FDA-approved Medication Assisted Treatments (MATS) especially Buprenorphine alone or in combination with Naloxone, Methadone and Naltrexone to treat both legal (iatrogenic) and illegal addiction to opiates /opioids including poly-drugs use seem counterintuitive.

In our opinion, although these drugs have a place in the very short term maybe six months for opiate replacement therapy and from 3- 7 days to help treat non-cancerous acute pain. However, utilizing these anti-reward substances that block the normal physiology of the brain –reward circuitry and adequate neuronal release of the chemical messenger dopamine, is like adding fuel to the fire.

With this said -“Is there a better solution”? To be honest, there is no simple answer and no “magic bullet” that will cure Reward Deficiency Syndrome (RDS) including both drug and non-drug related addictive behaviors. The complexity of how billions of neurons work to provide we homo sapiens with the remarkable ability to combat everyday stress and achieve intense pleasure was once a great mystery. Now modern genetics and neuroimaging techniques are providing a way to unravel how dysfunction in the reward circuitry of the brain ultimately leads to mental illness. The 2000 Nobel Prize Winner Eric Kandel stated:

“The brain is a complex biological organ possessing immense computational capability: it constructs our sensory experience, regulates our thoughts and emotions, and controls our actions.”

Since this statement is accepted as being true, how then, can a mortal person attempt to provide answers? These complex and highly emotional behavioral acts are, without oversimplification, what make us tick. In spite of this, here we are in the 21st century caught up in a global drug epidemic so vast and so pervasive that it is challenging our best scientific minds to find solutions.

RDS behaviors are all addictive compulsive and impulsive behaviors caused by dopamine dysregulation. How did we find out about RDS? The story of inheritable (genetic) or environmentally (epigenetic) induced RDS begins in the very late 60’s or early 70’s. At that time very little was known about the brain and especially about the chemical messengers involved in producing interaction within the brain’s nervous system that lead to human behaviors. Our first clue as to the role of the messenger chemical serotonin and alcohol intake is derived from the seminal work of Myers & Veale (1968) in lab rodents. They showed that desire (preference) to drink alcohol increased when the synthesis of serotonin was reduced in the brain. Another exciting finding published in Science in 1970 came from Virginia Davis and Michael Walsh. They found an alkaloid (Tetra-hydro-papaveroline) was produced in the brain of animals that consumed alcohol. This finding was important because it suggested that alcohol and opiate shared common mechanisms since this alkaloid a derivative of dopamine, is also found in the opiate producing poppy plant as the precursor to morphine. Blum’s group also showed that long-term drinking of alcohol (like 20 years on the street) significantly blocks the production of brain endorphins (the brain’s natural opiate). This work along with many other studies by a few scientists working in the addiction field inspired Blum’s laboratory to embark on some experiments starting in 1970 that framed the basis for a “commonality theory” between alcohol and opiates. This concept of common shared neurochemical mechanisms of two diverse substances alcohol and opiates sparked tremendous controversy. Blum’s group reported in Nature, the first evidence that the narcotic antagonist (blocker) Naloxone actually prevented alcohol dependence (1977). All this work led to the idea that “the junkie in the street seeking heroin is neurochemically similar to the executive drinking 5 martinis for lunch. “

The develpoment for a treatment for RDS began in 1978 with this concept of commonality. Seeking a way to raise brain endorphin levels (natural opioid peptides), Blum’s group, reported on a way to convert mice genetically bred to love alcohol – to hate alcohol, by raising brain endorphins. The amino –acid D-Phenylalanine was used to stop the enzyme which breaks down methionine-enkephalin.

Work in the mid 80’s by Dackis and Gold led to the idea especially in cocaine dependence of the “dopamine depletion hypothesis.” They attempted to replace the lost dopamine by directly stimulating one dopamine receptor called DRD2 using powerful Bromocriptine. This reduced acute cocaine craving, however, long-term use in test tube experiments caused a reduction in the number of dopamine receptors, resulting in an undesirable dysregulation of dopamine function. Gold’s group was correct in that normalizing dopamine particularly in the brain’s reward circuit as one promising treatment strategy consistent with recent animal models of dependence and previous theories about the role of Dopamine in addiction.
By 1984, the first generation of a complex KB220 reached over 1000 treatment centers in the United States with positive results. It is now in a liquid (aqua) nano form.

The challenge was to accomplish D2 receptor activation especially in the mesolimbic reward pathway with “gentle” dopamine agonist therapy. The second generation of the nutraceutical KB220Z
[see Table 1] was assembled based on the brain reward cascade [see Figure 1] which shows how the neurotransmitters serotonin, enkephalins, GABA, and dopamine interact to produce reward.

Table 1 Ingredients of the second generation of the nutraceutical KB220Z

Table 1 Ingredients of the second generation of the nutraceutical KB220Z

Figure 1 The Brain Reward Cascade

HOMEOSTASIS

Following many years of intensive research thirty studies have been now published showing the many clinical benefits of KB220. The following are highlights of some clinical outcomes of KB220 variations published in peer reviewed journals:

• Enhanced the brain enkephalin levels in rodents.
• Reduced alcohol-seeking behavior in alcohol loving C57/BL mice.
• Pharmacogenetic conversion from alcohol loving to alcohol hating DBA mice.
• Reduce drug (opiates) and alcohol withdrawal symptomatology reported in dependent humans.
• In a double-blind placebo controlled study reduced stress response, as measured by the skin conductance level (SCL) in recovering addicts.
• Patients in treatment during recovery in a double-blind –placebo controlled study had significantly improved Physical and BESS Scores (behavioral, emotional, social and spiritual).
• Following detox compared to placebo patients (both alcoholics and cocaine abusers) there was a six-fold decrease in Against Medical Advice (AMA) rates.
• A ten-month abstinent rate in DUI offenders 73% (alcoholics) and a 53% (cocaine dependent).
• Enhanced focus was demonstrated by healthy volunteers after 30 days of treatment.
• Reduced cravings for alcohol, heroin, cocaine, and nicotine have been shown.
• Reduced inappropriate sexual behavior demonstrated.
• Reduced post-traumatic stress (PTSD) symptoms, such as protracted alleviation of lucid nightmares, have been reported.
• Prolonged (12 months) elimination of life-long fearful lucid dreams.
• Reduced wide-spread theta power in the anterior cingulate cortex (where decisions are made) in both alcoholics and heroin addicts.
• Induction of enhanced alpha and low beta waves in anterior cingulate cortex of abstinent psychostimulant abusers using qEEG.
• In abstinent heroin addicts, fMRI investigation compared
to placebo a single dose increased resting state functional connectivity improved the prefrontal-cerebellar-occipital
neural network and activation of the NAc (Figure 2).Seemingly “dopamine Homeostasis”.
• In abstinent heroin addicts, compared to placebo a single dose reduced hyperactivity of the putamen potentially decreasing unwanted emotionality (Figure 2).

Figure 3 Human fMRI Placebo (Left) vs. KB220Z (Right) combined results five abstinent heroin addicts

Neuroimaging studies

• In obese patients, carriers of the D2 receptors A1 allele (30-40 % lowered D2 receptors) showed a significant Pearson correlation for enhanced compliance to days on treatment.
• Double-blinded controlled studies and others have demonstrated positive effects on both craving attenuation and relapse prevention.
• In Rodents, fMRI analysis compared to placebo significantly activates the left nucleus accumbens, cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and improved dopaminergic functionality was found across the brain reward circuitry (Figure 3).

Figure 3 Rat fMRI placebo (B) vs. KB220Z (C)

KB220Z A PRO

• An ADHD case study using LORETTA qEEG analysis revealed that after one dose the frequency of each band; in the anterior, dorsal and posterior cingulate regions, as well as the right dorsolateral prefrontal cortex increased during Working Memory.

In fact, it has been shown that a form of gene therapy that increases the number of D2 receptors (DNA-directed compensatory overexpression of the Dopamine D2 receptors) results in a significant reduction in alcohol and cocaine craving behavior in drug-preferring rodents. The basis of dependence on psychoactive substances is a “hyperdopaminergic state” as seen in alcohol withdrawal or due to other (epigenetic) environmental stressors or a “hypodopaminergic trait” due to the genetics of the brain reward circuitry.

The above preclinical and clinical results suggest that KB220 variants may help restore the required dopamine regulation(homeostasis). It is quite possible that utilization of this nutraceutical instead of highly abusable MATS should be considered as a frontline approach to treating Reward Deficiency Syndrome,
(functionally dopamine dysregulation), especially during recovery.
Wc1481
References Provided Upon Request

Kenneth Blum, B.Sc. (Pharmacy), M.Sc., Ph.D. & DHL; received
his Ph.D. in Neuropharmacology from New York Medical College
and graduated from Columbia University and New Jersey College
of Medicine. He also received a doctor of humane letters from Saint Martin’s University Lacey, WA. He has published more than 550 abstracts; peer-reviewed articles and 14-books.

John Giordano DHL, MAC is a counselor, President and Founder of the National Institute for Holistic Addiction Studies and Chaplain of the North Miami Police Department. For the latest development in cutting-edge treatment check out his website: http://www.holisticaddictioninfo.com

Lyle Fried graduated Magna Cum Laude with a Psychology degree from Liberty University. He is a Florida Board-Certified Addictions Professional (CAP); Internationally Certified Alcohol & Drug Counselor (ICADC); Board Member, Alliance for Addiction Solutions
(AAS); member of the International Substance Abuse & Addiction Coalition (ISAAC); an Approved Training Provider through the Florida Certification Board; and a member of the Florida Association of Drug Court Professionals. He currently works as Co-Founder/CEO of The Shores Treatment & Recovery.